A principle step in the process leading to muscle contraction is the intracellular release of calcium. Our objectives are to compare physical and chemical events that signal calcium release in contracting muscle cells, to describe the effects of agents that are believed to alter intracellular calcium release during muscle contraction, and to determine the mechanism of excitation-contraction (EC) coupling. Features indicative of calcium release will be corrected with changes in membrane potential, charge movements, and tension development in muscle cells. Physical features include striation spacing and myofibrillar orientation recorded by visible light microscopy and cine-photography. Chemical features include the relative change in intracellular calcium recorded as light emission from cells microinjected with calcium-sensitive photoprotein aequorin. Correlations among these variables will be used to evaluate the mechanism of action of agents that may change calcium release during EC coupling, and to evaluate models for EC coupling.